Many proteins are potentially useful in therapeutic drug applications. Nevertheless, controlled delivery of proteins remains a challenge, due in part to the fragile nature of some proteins (such as enzyme polypeptides) and the ability of proteins to diffuse. Sustained delivery of proteins while maintaining function is particularly desirable.
Layer-by-layer (LbL) absorption of oppositely charged polyelectrolytes on substrates can be used to fabricate thin multi-layer films for drug development. Nevertheless, LbL-based methods of delivering drugs were traditionally based on the formation of uniform films from which drug escapes via diffusion. Such diffusion-based release limits or eliminates the opportunity for controlled sequential delivery of drugs released from the surface to the surrounding medium. With such films, a typical diffusive, nonlinear drug release pattern is observed, and rarely is diffusion-controlled release from LbL films sustained for more than a few hours.
Because release time is impacted by the affinity of the drug for water, it is directly related to the hydrophobic nature of the drug, rather than an externally controlled parameter. Thus, releasing drugs by diffusion is not a useful strategy for all hydrophilic drugs, such as proteins. Other methods allow encapsulation of proteins within a shell of LbL coats for release under significant pH (pH 8 or higher) or ionic strength changes, nevertheless, this is impractical for many medical applications, as such large deviations from physiological conditions would be often deadly. Also, processing methods for such films typically involve harsh solvents, in addition to acidic byproducts of degradation, which may destroy the protein intended to be delivered.